MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the process of premetastatic niche formation is a crucial event according to modern concepts of tumour dissemination. The role of the present study was to investigate the expression levels of miR‐155, miR‐21, miR‐205 and miR‐let7b, as well as that of their target genes, in target organs of melanoma metastasis at the premetastatic stage. The expression levels of both the pro‐oncogenic miR‐155 and the tumour suppressive miR‐205 were found to be altered in the premetastatic liver of melanoma B16‐bearing mice. Bioinformatics analysis identified the target genes of miR‐155 to be nuclear factor, erythroid 2 like 2 (NFE2L2), secretogranin II, miR‐205, semaphorin 5A and vascular endothelial growth factor A (VEGFA). Among those, the redox status regulatory factor NFE2L2 was downregulated, which corresponded to increased levels of miR‐155. Due to the ability of pro‐oxidative events to initiate angiogenesis, VEGFA levels were evaluated in the premetastatic liver by immunohistochemistry, which revealed increased VEGFA expression in the central parts of the organ and diminished expression in the periphery. Taken together, these findings may support the concept of functional organ reorganization due to melanoma progression.

中文翻译：

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miR-155过度表达后，其靶基因NFE2L2下调，并且在转移前阶段荷黑素瘤B16小鼠肝脏中的VEGFA表达模式改变。

MicroRNA参与肿瘤进展的控制和转移级联动力学。然而，尽管根据现代的肿瘤传播概念，转移前小生境的形成过程是至关重要的事件，但microRNA在转移前阶段在远处器官重组中的作用尚不清楚。本研究的作用是调查转移前阶段黑色素瘤转移靶器官中miR‐155，miR‐21，miR‐205和miR‐let7b的表达水平及其靶基因的表达水平。发现在携带黑素瘤B16的小鼠的转移前肝脏中，致癌性miR-155和抑癌性miR-205的表达水平均发生了改变。生物信息学分析确定miR‐155的靶基因为核因子，类红细胞2（NFE2L2），促分泌素II，miR-205，semaphorin 5A和血管内皮生长因子A（VEGFA）。其中，氧化还原状态调节因子NFE2L2被下调，这与miR-155的水平升高相对应。由于促氧化事件能够引发血管生成，因此通过免疫组织化学评估了转移前肝脏中的VEGFA水平，该结果显示了器官中部的VEGFA表达增加而外周的表达减少。综上所述，这些发现可能支持由于黑色素瘤进展而导致的功能器官重组的概念。通过免疫组织化学对转移前肝脏中的VEGFA水平进行了评估，结果显示器官中部的VEGFA表达增加，而外围的表达减少。综上所述，这些发现可能支持由于黑色素瘤进展而导致的功能器官重组的概念。通过免疫组织化学对转移前肝脏中的VEGFA水平进行了评估，结果显示器官中部的VEGFA表达增加，而外围的表达减少。综上所述，这些发现可能支持由于黑色素瘤进展而导致的功能器官重组的概念。